A modified form of high dose rate (HDR) brachytherapy has been developed called Axxent Electronic Brachytherapy (EBT). EBT uses a kilovolt X-ray source and does not require treatment in a shielded vault or a HDR afterloader unit. A multi-center clinical study was carried out to evaluate the success of treatment delivery, safety and toxicity of EBT in patients with endometrial cancer.
A total of 15 patients with stage I or II endometrial cancer were enrolled at 5 sites. Patients were treated with vaginal EBT alone or in combination with external beam radiation.
The prescribed doses of EBT were successfully delivered in all 15 patients. From the first fraction through 3 months follow-up, there were 4 CTC Grade 1 adverse events and 2 CTC Grade II adverse events reported that were EBT related. The mild events reported were dysuria, vaginal dryness, mucosal atrophy, and rectal bleeding. The moderate treatment related adverse events included dysuria, and vaginal pain. No Grade III or IV adverse events were reported. The EBT system performed well and was associated with limited acute toxicities.
EBT shows acute results similar to HDR brachytherapy. Additional research is needed to further assess the clinical efficacy and safety of EBT in the treatment of endometrial cancer.
This retrospective, multicenter study evaluated the feasibility and safety of high-dose rate electronic brachytherapy (EBT) as a postsurgical adjuvant radiation therapy for endometrial cancer.
Medical records were reviewed from 41 patients (age 40–89 years) with endometrial cancer (Federation of International Gynecology and Obstetrics stages IA–IIIC) treated at nine centers between April 2008 and October 2009. Treatment included intracavitary vaginal EBT alone (n = l6) at doses of 18.0–24.0 Gy in 3–4 fractions and EBT in combination with external beam radiation therapy (EBRT, n = 25) at a total radiation dose range of 40.0–80.4 Gy. Doses were prescribed to a depth of 5 mm from the applicator surface and to the upper third (n = 15) and the upper half (n = 26) of the vagina.
Median follow-up was 3.8 (range 0.5–12.0) months. All 41 patients received the intended dose of radiation as prescribed. Adverse events occurred in 13 of 41 patients and were mild to moderate (Grade 1–2), consisting primarily of vaginal mucositis, rectal mucosal irritation and discomfort, and temporary dysuria and diarrhea. There were no Grade 3 adverse events in the EBT-only treatment group. One patient, who was being treated with the combination of EBT and EBRT for recurrent endometrial cancer, had a Grade 3 adverse event. No recurrences have been reported to date.
Electronic brachytherapy provides a feasible treatment option for postoperative adjuvant vaginal brachytherapy as sole radiation therapy and in combination with EBRT for primary endometrial cancer. Early and late toxicities were mild to moderate.
endometrial cancer; electronic brachytherapy; radiation therapy
Electronic brachytherapy (EBT) was developed to allow accelerated partial breast irradiation to be performed in a patient procedure room with minimal shielding. This observational, nonrandomized, multicenter study evaluated EBT as a post-surgical adjuvant radiation therapy for early stage breast cancer.
This study included women aged 50 years or more with invasive carcinoma or ductal carcinoma in situ, tumor size ≤3 cm, negative lymph node status, and negative surgical margins. The endpoints were skin and subcutaneous toxicities, efficacy outcomes, cosmetic outcomes, and device performance. In this interim report, 1-month, 6-month, and 1-year follow-up data are available on 68, 59, and 37 patients, respectively.
The EBT device performed consistently, delivering the prescribed 34 Gy to all 69 patients (10 fractions/patient). Most adverse events were Grade 1 and included firmness, erythema, breast tenderness, hyperpigmentation, pruritis, field contracture, seroma, rash/desquamation, palpable mass, breast edema, hypopigmentation, telangiectasia, and blistering, which were anticipated. Breast infection occurred in two (2.9%) patients. No tumor recurrences were reported. Cosmetic outcomes were excellent or good in 83.9%–100% of evaluable patients at 1 month, 6 months, and 1 year.
This observational, nonrandomized, multicenter study demonstrates that this EBT device was reliable and well tolerated as an adjuvant radiation therapy for early stage breast cancer.
radiation therapy; electronic brachytherapy; breast cancer
Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intra-operative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified.
Millions of people are diagnosed with non-melanoma skin cancers (NMSC) worldwide each year. While surgical approaches are the standard treatment, some patients are appropriate candidates for radiation therapy for NMSC. High dose rate (HDR) brachytherapy using surface applicators has shown efficacy in the treatment of NMSC and shortens the radiation treatment schedule by using a condensed hypofractionated approach. An electronic brachytherapy (EBT) system permits treatment of NMSC without the use of a radioactive isotope.
Data were collected retrospectively from patients treated from July 2009 through March 2010. Pre-treatment biopsy was performed to confirm a malignant cutaneous diagnosis. A CT scan was performed to assess lesion depth for treatment planning, and an appropriate size of surface applicator was selected to provide an acceptable margin. An HDR EBT system delivered a dose of 40.0 Gy in eight fractions twice weekly with 48 hours between fractions, prescribed to a depth of 3-7 mm. Treatment feasibility, acute safety, efficacy outcomes, and cosmetic results were assessed.
Thirty-seven patients (mean age 72.5 years) with 44 cutaneous malignancies were treated. Of 44 lesions treated, 39 (89%) were T1, 1 (2%) Tis, 1 (2%) T2, and 3 (7%) lesions were recurrent. Lesion locations included the nose for 16 lesions (36.4%), ear 5 (11%), scalp 5 (11%), face 14 (32%), and an extremity for 4 (9%). Median follow-up was 4.1 months. No severe toxicities occurred. Cosmesis ratings were good to excellent for 100% of the lesions at follow-up.
The early outcomes of EBT for the treatment of NMSC appear to show acceptable acute safety and favorable cosmetic outcomes. Using a hypofractionated approach, EBT provides a convenient treatment schedule.
Accelerated partial breast irradiation (APBI) may be used to deliver radiation to the tumor bed post-lumpectomy in eligible patients with breast cancer. Patient and tumor characteristics as well as the lumpectomy technique can influence patient eligibility for APBI. This report describes a lumpectomy procedure and examines patient, tumor, and surgical characteristics from a prospective, multicenter study of electronic brachytherapy.
The study enrolled 65 patients of age 45-84 years with ductal carcinoma or ductal carcinoma in situ, and 44 patients, who met the inclusion and exclusion criteria, were treated with APBI using the Axxent® electronic brachytherapy system following lumpectomy. The prescription dose was 34 Gy in 10 fractions over 5 days.
The lumpectomy technique as described herein varied by site and patient characteristics. The balloon applicator was implanted by the surgeon (91%) or a radiation oncologist (9%) during or up to 61 days post-lumpectomy (mean 22 days). A lateral approach was most commonly used (59%) for insertion of the applicator followed by an incision site approach in 27% of cases, a medial approach in 5%, and an inferior approach in 7%. A trocar was used during applicator insertion in 27% of cases. Local anesthetic, sedation, both or neither were administered in 45%, 2%, 41% and 11% of cases, respectively, during applicator placement. The prescription dose was delivered in 42 of 44 treated patients.
Early stage breast cancer can be treated with breast conserving surgery and APBI using electronic brachytherapy. Treatment was well tolerated, and these early outcomes were similar to the early outcomes with iridium-based balloon brachytherapy.
Purpose. To assess for differences in clinical, radiologic, and pathologic outcomes between patients with stage II-III rectal adenocarcinoma treated neoadjuvantly with conventional external beam radiotherapy (3D conformal radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT)) versus high-dose-rate endorectal brachytherapy (EBT). Methods. Patients undergoing neoadjuvant EBT received 4 consecutive daily 6.5 Gy fractions without chemotherapy, while those undergoing 3DRT or IMRT received 28 daily 1.8 Gy fractions with concurrent 5-fluorouracil. Data was collected prospectively for 7 EBT patients and retrospectively for 25 historical 3DRT/IMRT controls. Results. Time to surgery was less for EBT compared to 3DRT and IMRT (P < 0.001). There was a trend towards higher rate of pathologic CR for EBT (P = 0.06). Rates of margin and lymph node positivity at resection were similar for all groups. Acute toxicity was less for EBT compared to 3DRT and IMRT (P = 0.025). Overall and progression-free survival were noninferior for EBT. On MRI, EBT achieved similar complete response rate and reduction in tumor volume as 3DRT and IMRT. Histopathologic comparison showed that EBT resulted in more localized treatment effects and fewer serosal adhesions. Conclusions. EBT offers several practical benefits over conventional radiotherapy techniques and appears to be at least as effective against low rectal cancer as measured by short-term outcomes.
Accelerated partial breast irradiation (APBI) with high dose rate (HDR) brachytherapy offers an excellent compact course of radiation due to its limited number of fractions for early-stage carcinoma of breast. One of the recent devices is SAVI (strut-adjusted volume implant), which has 6, 8 or 10 peripheral source channels with one center channel. Each channel can be differentially loaded. This paper focuses on the treatment planning, dosimetry and quality assurance aspects of HDR brachytherapy implant with GammaMed Plus HDR afterloader unit. The accelerated PBI balloon devices normally inflate above 35 cc range, and hence these balloon type devices cannot be accommodated in small lumpectomy cavity sizes. CT images were obtained and 3-D dosimetric plans were done with Brachyvision planning system. The 3-D treatment planning and dosimetric data were evaluated with planning target volume (PTV)_eval V90, V95, V150, V200 skin dose and minimum distance to skin. With the use of the SAVI 6-1 mini device, we were able to accomplish an excellent coverage — V90, V95, V150 and V200 to 98%, 95%, 37 cc (<50 cc volume) and 16 cc (<20 cc volume), respectively. Maximum skin dose was between 73% and 90%, much below the prescribed dose of 34 Gy. The minimum skin distance achieved was 5 to 11 mm. The volume that received 50% of the prescribed radiation dose was found to be lower with SAVI. The multi-channel SAVI-based implants reduced the maximum skin dose to markedly lower levels as compared to other modalities, simultaneously achieving best dose coverage to target volume. Differential-source dwell-loading allows modulation of the radiation dose distribution in symmetric or asymmetric opening of the catheter shapes and is also advantageous in cavities close to chest wall.
Accelerated partial breast irradiation; high dose rate; SAVI
Post-operative radiotherapy has commonly been used for early stage breast cancer to treat residual disease. The primary objective of this work was to characterize, through dosimetric and radiobiological modeling, a novel focal brachytherapy technique which uses direct intracavitary infusion of β-emitting radionuclides (186Re/188Re) carried by lipid nanoparticles (liposomes). Absorbed dose calculations were performed for a spherical lumpectomy cavity with a uniformly injected activity distribution using a dose point kernel convolution technique. Radiobiological indices were used to relate predicted therapy outcome and normal tissue complication of this technique with equivalent external beam radiotherapy treatment regimens. Modeled stromal damage was used as a measure of the inhibition of the stimulatory effect on tumor growth driven by the wound healing response. A sample treatment plan delivering 50 Gy at a therapeutic range of 2.0 mm for 186Re-liposomes and 5.0 mm for 188Re-liposomes takes advantage of the dose delivery characteristics of the β-emissions, providing significant EUD (58.2 Gy and 72.5 Gy for 186Re and 188Re, respectively) with a minimal NTCP (0.046%) of the healthy ipsilateral breast. Modeling of kidney BED and ipsilateral breast NTCP showed that large injected activity concentrations of both radionuclides could be safely administered without significant complications.
Conformal dose coverage for accelerated partial breast irradiation or radiotherapy boost can be obtained with AccuBoost® D-shaped brachytherapy applicators using a flattened surface positioned near the patient. Three D-shaped applicators (D45/D53/D60) were dosimetrically characterized using Monte Carlo methods (MCNP5), air ionization chambers (Farmer and Markus), and radiochromic film (GafChromic EBT) in polystyrene and ICRU 44 breast tissue. HDR 192Ir source dwell times were either constant or optimized to improve skin dose uniformity. Scatter dose decreased as depth decreased. 10 mm beyond the applicator aperture, dose reductions of 90% and 51% were observed at depths of 0 and 30 mm, respectively. Similarly, planar dose uniformity improved as depth decreased and was also due to scatter and applicator geometry. Dose uniformity inside the applicator aperture was approximately 11% and 15% for all three applicators at the skin and 30 mm deep, respectively. Depth dose measurements in polystyrene using ion chamber and radiochromic film agreed with Monte Carlo results within 2%. Discrepancies between film and Monte Carlo dose profiles at 30 mm depth were within 1%.
Iridium-192 is widely used for high-dose rate brachytherapy. Co-60 source with similar geometric and dosimetric properties are now available. It has a longer half life but higher energy than Iridium-192. If Co-60 source can produce similar results, it will be more economical for low resource settings.
To evaluate the acute gastrointestinal and genitourinary toxicity associated with Co-60 source in the brachytherapy of cervical cancer.
Seventy patients with cervical cancer received 45 Gy in 22 fractions of pelvic external beam radiotherapy and 19.5 Gy in 3 fractions of HDR with Co-60 source using tandem and ring applicators with 6 courses of cisplatin 50 mg/m2 and 5 fluorouracil 1000 mg/m2 every 3 weeks Toxicity was scored using NCI-CTC version 4.0.
The median total BED (Gy10) for tumor was 86.2 (84.4–88.8) while that for rectum (BED Gy3) was 124.4 (120–133). Two patients (3%) had grade 3 gastrointestinal toxicity while all others had ≤grade 2 toxicity and this is comparable with previous results.
Co-60 as HDR brachytherapy source is tolerable and is economical for low resource settings.
HDR brachytherapy; Co-60 source; cervical cancer; acute toxicity
Radical radiotherapy is one of the options for the management of prostate cancer. In external beam therapy, 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) are the options for delivery of increased radiation dose, as vital organs are very close to the prostate and a higher dose to these structures leads to an increased toxicity. In brachytherapy, low dose rate brachytherapy with permanent implant of radioactive seeds and high dose rate brachytherapy (HDR) with remote after loaders are available. A dosimetric analysis has been made on IMRT and HDR brachytherapy plans. Ten cases from each IMRT and HDR brachytherapy have been taken for the study. The analysis includes comparison of conformity and homogeneity indices, D100, D95, D90, D80, D50, D10 and D5 of the target. For the organs at risk (OAR), namely rectum and bladder, V100, V90 and V50 are compared. In HDR brachytherapy, the doses to 1 cc and 0.1 cc of urethra have also been studied. Since a very high dose surrounds the source, the 300% dose volumes in the target and within the catheters are also studied in two plans, to estimate the actual volume of target receiving dose over 300%. This study shows that the prescribed dose covers 93 and 92% of the target volume in IMRT and HDR brachytherapy respectively. HDR brachytherapy delivers a much lesser dose to OAR, compared to the IMRT. For rectum, the V50 in IMRT is 34.0cc whilst it is 7.5cc in HDR brachytherapy. With the graphic optimization tool in HDR brachytherapy planning, the dose to urethra could be kept within 120% of the target dose. Hence it is concluded that HDR brachytherapy may be the choice of treatment for cancer of prostate in the early stage.
Brachytherapy; conformity; intensity modulated radiotherapy; prostate
The aim of this study is to evaluate the decrease of biological equivalent dose and its correlation with local/loco-regional control of tumour in the treatment of cervical cancer when the strength of the Ir-192 high dose rate (HDR) brachytherapy (BT) source is reduced to single, double and triple half life in relation to original strength of 10 Ci (∼ 4.081 cGy x m2 x h−1).
Material and methods
A retrospective study was carried out on 52 cervical cancer patients with stage II and III treated with fractionated HDR-BT following external beam radiation therapy (EBRT). International Commission on Radiation Units and Measurement (ICRU) points were defined according to ICRU Report 38, using two orthogonal radiograph images taken by Simulator (Simulix HQ). Biologically effective dose (BED) was calculated at point A for different Ir-192 source strength and its possible correlation with local/loco-regional tumour control was discussed.
The increase of treatment time per fraction of dose due to the fall of dose rate especially in HDR-BT of cervical cancer results in reduction in BED of 2.59%, 7.02% and 13.68% with single, double and triple half life reduction of source strength, respectively. The probabilities of disease recurrence (local/loco-regional) within 26 months are expected as 0.12, 0.12, 0.16, 0.39 and 0.80 for source strength of 4.081, 2.041, 1.020, 0.510 and 0.347 cGy x m2 x h−1, respectively. The percentages of dose increase required to maintain the same BED with respect to initial BED were estimated as 1.71, 5.00, 11.00 and 15.86 for the dose rate of 24.7, 12.4, 6.2 and 4.2 Gy/hr at point A, respectively.
This retrospective study of cervical cancer patients treated with HDR-BT at different Ir-192 source strength shows reduction in disease free survival according to the increase in treatment time duration per fraction. The probable result could be associated with the decrease of biological equivalent dose to point A. Clinical end point of this study is more significant from double half life reduction of original source strength.
HDR brachytherapy; cervical cancer; biological effective dose; dose rate
The optimal dosimetric parameters and planning techniques for high-dose-rate vaginal brachytherapy (HDR-VB) are unclear. Our aim was to evaluate the utility of bladder and rectal dosimetry for patients receiving HDR-VB for postoperative treatment of endometrial carcinoma.
Material and methods
Patients with endometrial cancer who underwent postoperative HDR-VB from January 1, 2004 through December 31, 2010 were included. All patients underwent primary surgery consisting of total hysterectomy and bilateral salpingo-oophrectomy (TH-BSO) with or without lymph node dissection and were treated with HDR-VB without pelvic external beam radiotherapy (EBRT) or chemotherapy. Demographic, pathologic, dosimetric and clinical data were collected.
One hundred patients were identified with the majority of patients receiving HDR-VB in 700 cGy × 3 fractions (45%) or 550 cGy x 4 fractions (53%). No plan was altered based on bladder dosimetry at the time of planning. The rate of acute urinary reactions (< 90 days from beginning of RT) grades 1 and 2 were 14% and 2%, respectively. The rate of late urinary reactions (> 90 days after RT) grades 1 and 2 were 7% and 3%, respectively. Dose to the bladder point did not correlate with urinary toxicity. No rectal toxicity was reported by patients receiving HDR-VB.
In the setting of HDR-VB without EBRT, the measured dose to the bladder point does not predict urinary toxicity and is very unlikely to indicate the need to change the treatment plan. The treatment of endometrial carcinoma utilizing HDR-VB alone is associated with very low rates of high-grade acute or late bladder toxicity.
endometrial cancer; high-dose-rate; brachytherapy
RTOG 95-17 is a prospective Phase II cooperative group trial of APBI alone using multicatheter brachytherapy following lumpectomy in select early stage breast cancers. Tumor control and survival outcomes are reported.
Materials and Methods:
Eligibility criteria included stage I/II breast carcinoma confirmed to be <3cm, unifocal, invasive non-lobular histology with 0-3 positive axillary nodes without extracapsular extension. APBI treatment was delivered with either Low Dose Rate (LDR) (45 Gy in 3.5-5 days) or High Dose Rate (HDR) (34 Gy in 10 BID fractions over 5 days). Endpoints evaluated included in-breast control, regional control, mastectomy-free rate, mastectomy-free survival, disease-free survival and overall survival. The study was designed to analyze the HDR and LDR groups separately and without comparison.
Between 1997 and 2000, 100 patients were accrued and 99 were eligible; 66 treated with HDR and 33 treated with LDR. Eighty seven patients had T1 lesions and 12 had T2 lesions. Seventy nine were pathologically N0 and 20 were N1. Median follow-up in the HDR group is 6.14 years with the 5-year estimates of in-breast, regional and contralateral failure rates of 3%, 5% and 2%, respectively. The LDR group experienced similar results with a median follow-up of 6.22 years. The 5-year estimates of in-breast, regional and contralateral failure rates of 6%, 0% and 6%, respectively.
Patients treated with multicatheter partial breast brachytherapy on this trial experienced excellent in-breast control rates and overall outcome that compare to reports from APBI studies with similar extended follow-up.
Brachytherapy; breast cancer; breast cancer trials; radiation therapy for breast cancer; accelerated partial breast irradiation
To estimate the rate of late grade 3 or greater genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) following treatment with external beam radiation therapy and prostate high dose rate (HDR) brachytherapy.
Methods and Materials
Each participating institution submitted CT based HDR brachytherapy dosimetry data electronically for credentialing and for each study patient. Patients with locally confined T1c-T3b prostate cancer were eligible for this study. All patients were treated with 45 Gy in 25 fractions from external beam radiotherapy and one HDR implant delivering 19 Gy in 2 fractions. All AEs were graded according to CTCAEv3.0. Late GU/ GI AEs were defined as those occurring more than nine months from the start of the protocol treatment, in patients with at least 18 months of potential follow-up.
A total of 129 patients from 14 institutions were enrolled in this study. 125 patients were eligible and AE data was available for 112 patients. The pretreatment characteristics of the patients were as follows: T1c-T2c 91%, T3a-T3b 9%, PSA ≤ 10 70%, PSA >10-≤20 30%, GS 2-6 10%, GS 7 72%, and GS 8-10 18%. At a median follow-up time of 29.6 months, 3 acute and 4 late grade 3 GU/GI AEs were reported. The estimated rate of late grade 3-5 GU and GI AE at 18 months was 2.56%.
This is the first prospective, multi-institutional trial of CT based HDR brachytherapy and external beam radiotherapy. The technique and doses used in this study resulted in acceptable levels of adverse events.
Prostate cancer; High Dose Rate; Brachytherapy; Prospective multi-institutional clinical trial
The literature supporting high-dose rate brachytherapy (HDR) in the treatment of cervical carcinoma derives primarily from retrospective series. However, controversy still persists regarding the efficacy and safety of HDR brachytherapy compared to low-dose rate (LDR) brachytherapy, in particular, due to inadequate tumor coverage for stage III patients. Whether LDR or HDR brachytherapy produces better results for these patients in terms of survival rate, local control rate and the treatment complications remain controversial.
A meta-analysis of RCT was performed comparing LDR to HDR brachytherapy for cervix cancer treated for radiotherapy alone. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, as well as abstracts published in the annual proceedings were systematically searched. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We used "recommend" for strong recommendations, and "suggest" for weak recommendations.
Pooled results from five randomized trials (2,065 patients) of HDR brachytherapy in cervix cancer showed no significant increase of mortality (p = 0.52), local recurrence (p = 0.68), or late complications (rectal; p = 0.7, bladder; p = 0.95 or small intestine; p = 0.06) rates as compared to LDR brachytherapy. In the subgroup analysis no difference was observed for overall mortality and local recurrence in patients with clinical stages I, II and III. The quality of evidence was low for mortality and local recurrence in patients with clinical stage I, and moderate for other clinical stages.
Our meta-analysis shows that there are no differences between HDR and LDR for overall survival, local recurrence and late complications for clinical stages I, II and III. By means of the GRADE system, we recommend the use of HDR for all clinical stages of cervix cancer.
To investigate the efficacy and safety of accelerated partial breast irradiation (APBI) via high-dose-rate (HDR) multicatheter interstitial brachytherapy for early-stage breast cancer.
Between 2002 and 2006, 48 prospectively selected patients with early-stage breast cancer received APBI using multicatheter brachytherapy following breast-conserving surgery. Their median age was 52 years (range 36-78). A median of 34 Gy (range 30-34) in 10 fractions given twice daily within 5 days was delivered to the tumor bed plus a 1-2 cm margin. Most (92%) patients received adjuvant systemic treatments. The median follow-up was 53 months (range 36-95). Actuarial local control rate was estimated from surgery using Kaplan-Meier method.
Local recurrence occurred in two patients. Both were true recurrence/marginal miss and developed in patients with close (< 0.2 cm) surgical margin after 33 and 40 months. The 5-year actuarial local recurrence rate was 4.6%. No regional or distant relapse and death has occurred to date. Late Grade 1 or 2 late skin and subcutaneous toxicity was seen in 11 (22.9%) and 26 (54.2%) patients, respectively. The volumes receiving 100% and 150% of the prescribed dose were significantly higher in the patients with late subcutaneous toxicity (p = 0.018 and 0.034, respectively). Cosmesis was excellent to good in 89.6%.
APBI using HDR multicatheter brachytherapy yielded local control, toxicity, and cosmesis comparable to those of conventional whole breast irradiation for select early-stage breast cancer. Patients with close resection margins may be ineligible for APBI.
Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.
brachytherapy; oral cancer; high dose rate
To investigate the dosimetric impact of point A definitions on both conventional point A plans and MRI-guided conformal high-dose-rate (HDR) brachytherapy plans.
Material and methods
Fifty-five HDR plans of 36 patients with FIGO stage I to IV cervical cancer were retrospectively studied; these included 30 conventional treatments and 25 conformal plans. Two different point A definitions were explored: the revised Manchester point A and the new point A as recommended by the American Brachytherapy Society. Conventional plans were produced by varying only the point A definition and the normalized isodose lines. Conformal plans were retrospectively generated per GEC-ESTRO recommendations based upon 3.0 Tesla MRI data.
Small yet significant variations were found in point A locations (mean: 0.5 cm, maximum: 2.1 cm, p < 0.001). The use of a new point A caused minimal dose variation for both conventional and conformal plans. Conventional plans normalized to the new point A generated up to 12% (avg. 1-3%) higher overall dose in terms of higher total reference air kerma than plans normalized to other points. Dosimetric changes due to point A definitions were up to 11-12% (avg. less than 2%) on target volumes or organs-at-risk.
For both conventional and conformal plans, the new point A definition leads to smaller variations caused during implant and/or differences in patient anatomy. Using the new point A is expected to produce more consistent brachytherapy plans and improve outcome analysis.
brachytherapy; cervical cancer; high-dose-rate brachytherapy; MRI-guided; point A
To evaluate local control, survival and toxicity in patients with early-stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) alone using a novel low dose regimen
We reviewed records of 414 patients with stage IA to stage II endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157 patients with endometrioid histology received 24 Gy in 6 fractions of HDR vaginal cylinder brachytherapy and constitute the study population. Dose was prescribed at the cylinder surface and delivered twice weekly in the post-operative setting. Local control and survival rates were calculated by the Kaplan-Meier method.
All 157 patients completed the prescribed course of VB. Median follow-up time was 22.8 months (range, 1.5–76.5). Two patients developed vaginal recurrence, one in the periurethral region below the field and one in the fornix after treatment with a 2.5-cm cylinder. Three patients developed regional recurrence in the para-aortic region. Two patients developed distant metastasis (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%, locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal, genitourinary or skin long-term toxicity was reported for any patient.
Vaginal brachytherapy alone in early-stage endometrial cancer provides excellent results in terms of locoregional control and disease-free survival. The fractionation scheme of 24 Gy in 6 fractions prescribed to the cylinder surface was well-tolerated with minimal late toxicity.
Endometrial cancer; vaginal brachytherapy; high-dose-rate
Brachytherapy is a radiation treatment that uses an implanted radioactive source. In recent years, use of breast brachytherapy after lumpectomy for early breast cancer has increased substantially despite a lack of randomized trial data comparing its effectiveness with standard whole-breast irradiation (WBI). Because results of long-term randomized trials will not be reported for years, detailed analysis of clinical outcomes in a nonrandomized setting is warranted.
To compare the likelihood of breast preservation, complications, and survival for brachytherapy vs WBI among a nationwide cohort of older women with breast cancer with fee-for-service Medicare.
Retrospective population-based cohort study of 92 735 women aged 67 years or older with incident invasive breast cancer, diagnosed between 2003 and 2007 and followed up through 2008. After lumpectomy 6952 patients were treated with brachytherapy vs 85 783 with WBI.
Main Outcome Measures
Cumulative incidence and adjusted risk of subsequent mastectomy (an indicator of failure to preserve the breast) and death were compared using the log-rank test and proportional hazards models. Odds of postoperative infectious and noninfectious complications within 1 year were compared using the χ2 test and logistic models. Cumulative incidences of long-term complications were compared using the log-rank test.
Five-year incidence of subsequent mastectomy was higher in women treated with brachytherapy (3.95%; 95% CI, 3.19%–4.88%) vs WBI (2.18%; 95% CI, 2.04%–2.33%; P<.001) and persisted after multivariate adjustment (hazard ratio [HR], 2.19; 95% CI, 1.84–2.61, P<.001). Brachytherapy was associated with more frequentinfectious (16.20%; 95% CI, 15.34%–17.08% vs 10.33%; 95% CI, 10.13%–10.53%; P<.001; adjusted odds ratio [OR], 1.76; 1.64–1.88) and noninfectious (16.25%; 95% CI, 15.39%–17.14% vs 9.00%; 95% CI, 8.81%–9.19%; P<.001; adjusted OR, 2.03; 95% CI, 1.89–2.17) postoperative complications; and higher 5-year incidence of breast pain (14.55%, 95% CI, 13.39%–15.80% vs 11.92%; 95% CI, 11.63%–12.21%), fat necrosis (8.26%; 95% CI, 7.27–9.38 vs 4.05%; 95% CI, 3.87%–4.24%), and rib fracture (4.53%; 95% CI, 3.63%–5.64% vs 3.62%; 95% CI, 3.44%–3.82%; P≤.01 for all). Five-year overall survival was 87.66% (95% CI, 85.94%–89.18%) in patients treated with brachytherapy vs 87.04% (95% CI, 86.69%–87.39%) in patients treated with WBI (adjusted HR, 0.94; 95% CI, 0.84–1.05; P=.26).
In a cohort of older women with breast cancer, treatment with brachytherapy compared with WBI was associated with worse long-term breast preservation and increased complications but no difference in survival.
To induce fast relief of dysphagia in patients with oesophageal cancer high dose rate (HDR) brachytherapy was applied before external radiotherapy in a prospective study. Seventy-four patients with inoperable oesophageal cancer (36 squamous cell, 38 adenocarcinoma) were treated with a combination of 10 Gy HDR brachytherapy, followed by 40 Gy in 4 weeks external beam radiotherapy (EBRT), starting 2 weeks later. Tumour response, as measured by endoscopy and/or barium swallow, revealed complete remission in 21 and partial response in 38 patients (overall response rate 80%). Improvement of dysphagia was induced by brachytherapy within a few days in 39%, and achieved at the end of treatment in 70% of patients. Further weight loss was prevented in 39 of the 59 patients who presented with weight loss. Pain at presentation improved in 12 out of 25 patients. Median survival was 9 months. No differences in either response rate or survival were found in squamous cell or adenocarcinoma. Side-effects were either acute with minimal discomfort in 32 (42%) or late with painful ulceration in five patients (7%), occurring after a median of 4 months. A fistula developed in six patients, all with concurrent tumour. In conclusion, brachytherapy before EBRT was a safe and effective procedure to induce rapid relief of dysphagia, especially when combined with EBRT.
A study was conducted to determine the dosimetric effects resulting from air pockets and high atomic number (Z) contrast medium within a multichannel breast brachytherapy device.
Material and methods
A 5-6 cm diameter Contura (SenoRx) brachytherapy device was inflated using 37 cm3 of saline. Baseline dose falloff from an HDR Iridium-192 source was measured with the Iridium source centered in the central channel and an anterior off-center channel. Data were collected at distances from 1 to 50 mm. Comparison studies were conducted with identically inflated volume containing varied air pocket volumes (1-4 cm3) and concentrations of contrast solution (3%, 6%, and 9% by volume). Dose perturbation factors (DPF) were computed and evaluated.
Dose perturbations due to air pockets and contrast solutions were observed. As the volume of air increased, the DPF increased by approximately 2.25%/cm3. The effect was consistent for both channels. The contrast effects were more complex. The 3% contrast media had minimal dose perturbation. The 6% contrast solution caused dose reduction of 1.0% from the central channel but 1.5% dose increase from the anterior channel. The 9% contrast solution caused dose reductions by 4.0% (from central channel) and 3.0% (from anterior channel). The DPF from all contrast solutions moderated with increasing distance.
Dose perturbations due to air pockets and high-Z contrast solution can be significant. It is important to control these effects to avoid dose errors.
brachytherapy; breast cancer; dose perturbation; PBI
To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost.
Materials and methods
Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml.
Median follow-up was 24 months (range 18–36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6.
We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive.